摘要
新突发病毒性传染病已在全球引起多起疫情的暴发流行,对人类健康、社会稳定和经济发展等造成了严重而深远的影响.目前,疫苗、小分子药物及抗体是预防和治疗新突发病毒性传染病的重要手段,但这些防治手段在实际应用过程中仍面临一些严峻的挑战,因而有必要快速开发一种新型的抗病毒策略.核酸抗体是指将编码特异性中和抗体的mRNA或DNA分子通过递送载体引入体内,然后利用宿主细胞的蛋白质合成机制来表达相应的抗体,进而发挥中和病毒的作用.核酸抗体作为一种新型的生物制剂,其制备工艺简单、易实现快速和大规模生产、应用范围广且便于储存和运输,因而在新突发病毒性传染病防治方面具有良好的应用前景.为此,本文主要综述了核酸抗体的原理及在抗病毒防治中的研究现状,重点阐明了核酸抗体的优势和不同核酸抗体类型的优缺点及其在未来发展中可能面临的严峻挑战和应对策略,以期为核酸抗体在新突发病毒性传染病防治中的应用提供新的研究思路.
Emerging viral infectious diseases are diverse,fast-spreading and dangerous and have caused many outbreaks and epidemics worldwide,with serious and far-reaching effects on human health,social stability and economic development.At present,vaccines,small-molecule drugs and monoclonal antibodies(mAbs)are important tools for addressing new outbreaks of viral infectious diseases and have played key roles in the prevention and treatment of multiple viral infectious diseases.In particular,mAbs can effectively prevent a virus from entering host cells and block reinfection by progeny virus.mAbs can also facilitate the clearance of viruses and virus-infected cells via Fc-mediated effector functions.In addition,the effects of mAbs are related to several characteristics,such as their high specificity,ability to enhance immune responses and low toxicity.Thus,mAbs are appealing as potential therapeutics and prophylactics for viral infections.However,traditional mAb technology still has some limitations,such as complex production processes,high quality control requirements,high manufacturing costs,high treatment costs,and the need for strict cold chain storage and transportation,making it unsuitable for large-scale population use.Unfortunately,to date,only a small number of mAb drugs have been used to treat or prevent infectious diseases.Therefore,there is a need to rapidly develop a novel antiviral tool.As a type of novel biological agent,nucleic acid-encoded antibodies are DNA and mRNA molecules that encode virusspecific neutralizing antibodies that are appropriately sequenced and optimally regulated to obtain stably expressed DNA and mRNA molecules in vitro,which are then introduced into a host through a special delivery vehicle.Then,the host cells are used as individual bioreactors,and the protein synthesis mechanism is used to express structurally and functionally intact antibodies,which in turn act as neutralizing agents in vivo.Compared to traditional mAbs,nucleic acid-encoded antibodies have many potential advantages,such as ease and speed of design and testing,ease of rapid scale-up and manufacturing,ease of storage and transportation,and cost-effectiveness;consequently,they are considered an ideal alternative to traditional mAb technology.At present,nucleic acid-encoded antibodies have been used in preclinical studies on diseases caused by many viruses,such as human immunodeficiency virus,influenza virus,Chikungunya virus,Zika virus and SARS-CoV-2.Specifically,three nucleic acid-encoded antibodies have entered phase I clinical trials and have promising applications in the prevention and treatment of emerging viral infectious diseases.In this paper,we summarize the principles and current research status of nucleic acid-encoded antibodies in antiviral control and highlight the advantages of nucleic acid-encoded antibodies over traditional protein antibodies,the advantages and disadvantages of different nucleic acid-encoded antibodies,and the potential challenges and possible strategies for the future development of these agents to provide new research ideas for the application of nucleic acid-encoded antibodies in the control of future emerging viral infectious diseases.
作者
赵锁群
迟航
秦成峰
邓永强
Suoqun Zhao;Hang Chi;Chengfeng Qin;Yongqiang Deng(State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,Beijing 100071,China)
出处
《科学通报》
EI
CAS
CSCD
北大核心
2023年第15期1906-1916,共11页
Chinese Science Bulletin
基金
国家自然科学基金(82151222)资助。
关键词
新突发病毒性传染病
核酸抗体
DNA抗体
mRNA抗体
递送载体
emerging viral infectious diseases
nucleic acid-encoded antibodies
DNA-encoded antibodies
mRNA-encoded antibodies
delivery vectors
作者简介
联系人:邓永强,E-mail:dengyq1977@126.com。
